Research has linked depression with morbidity and mortality from chronic medical conditions. Given findings that depression is a mediator of smoking relapse, cigarette smoking provides fertile ground for research in this area. Smokers with a history of major depressive disorder (MDD) represent a significant proportion of smokers; these individuals experience more depressive symptoms upon cessation and higher relapse rates than other smokers. The proposed study will test the hypothesis that intensive treatment(s) intended to address depressive symptoms and negative mood will enhance the achievement and maintenance of smoking cessation in adult smokers with a history MDD. We will also examine the relationship between mood-related symptoms and smoking cessation outcomes. Finally, we will identify cognitive and behavioral mediators of the effects of depressive symptoms on smoking cessation. The study employs an additive randomized, double-blind, placebo-controlled design to test the incremental efficacy of: 1) standard smoking cessation treatment plus placebo, vs. 2) standard smoking cessation plus intensive cognitive- behavioral treatment for depression plus placebo, vs. 3) standard smoking cessation plus intensive cognitive-behavioral treatment for depression plus antidepressant (bupropion hydrochloride). All smokers will receive 14 group sessions of standard smoking cessation treatment, which includes 8 weeks of transdermal nicotine replacement. A sample of 396 subjects will be recruited to include only smokers with a positive history of MMD. Subjects will be treated for 12 weeks and followed for 12 months. Current and past psychiatric diagnoses will be assessed, as will changes in depressive symptoms and mood states. Smoking cessation outcomes will be validated by saliva cotinine. We expect that this study will result in the development of a specialized, efficacious treatment for the large percentage of smokers with past MMD, and will therefore have important clinical and public health significance in reducing the overall prevalence of cigarette smoking. We further expected that this study will increase our basic knowledge about the role of depressive symptoms, the effects of selected cognitive and behavioral mediators, and the interaction of pharmacological and psychosocial factors in the process of smoking cassation.